Evaluation of Neurotoxicity of NBOH Derivatives
Rodrigo Foss da Silva, Lennon Machado Alves, Fernanda Conte, Bruno Pereira Dos Santos, Rodrigo Ligabue‐braun, Solange Cristina García, Tiago Franco de Oliveira, Hecson Jesser Segat, Silvana Peterini Boeira, Dieniffer Espinosa Janner, Ana Cristina Correa Carvalhal Ferreira, Ariane Correa Carvalhal Ferreira, Marcelo Dutra Arbo
Pharmaceuticals July 8, 2026 Peer reviewed DOI: 10.3390/ph19071055 via OpenAlex
Summary
The study found that the NBOH derivatives 25E-NBOH and 25B-NBOH decreased cell viability in SH-SY5Y cells and caused mitochondrial hyperpolarization along with increased oxidative species at higher concentrations. In Drosophila melanogaster, 25B-NBOH increased climbing time, while both 25E-NBOH and 25B-NBOH enhanced catalase and acetylcholinesterase activities at 50 nM. The findings suggest that these compounds exhibit greater toxicity than 25I-NBOH, implicating metabolic activity, oxidative stress, and cholinergic dysregulation in their neurotoxicity.
Study at a glance
| Population | differentiated SH-SY5Y cells and Drosophila melanogaster flies |
|---|---|
| Key finding | Both 25E-NBOH and 25B-NBOH decreased cell viability and exhibited greater toxicity compared to 25I-NBOH. |
Abstract
Background/Objectives: The study sought to investigate the neurotoxicity of NBOHs, which are a class of new psychoactive substances (NPSs) that act as agonists of serotonin 5-HT2A and 5-HT2C receptors, resulting in hallucinogenic effects similar to those of LSD, often found in paper blotters. Methods: Differentiated SH-SY5Y cells were incubated for 24 h with 0.5, 1.0, 3.5, 5 and 10 nM of the derivatives 25I-NBOH, 25E-NBOH and 25B-NBOH. Cell viability was assessed by MTT reduction and neutral red uptake assays. Mitochondrial membrane potential and production of free radicals were also evaluated. In addition, Drosophila melanogaster flies were exposed to 5, 10 and 50 nM of each NBOH derivative for 4 h. Negative geotaxis, CAT, and AChE enzymatic activities were evaluated. Results: Both 25E-NBOH and 25B-NBOH decreased cell viability. Furthermore, mitochondrial hyperpolarization of cells and an increase in oxidative species were observed in response to higher concentrations of 25E-NBOH and 25B-NBOH. In D. melanogaster, 25B-NBOH increased climbing time and both 25E-NBOH and 25B-NBOH increased CAT and AChE activities at 50 nM. Conclusions: These findings indicate greater toxicity of the 25E- and 25B-NBOH compared to 25I-NBOH, suggesting metabolic activity or mitochondrial signaling, oxidative stress, and cholinergic dysregulation as a potential mechanism related to NBOH neurotoxicity.